Transdermal estrogen device and delivery

Abstract

Described are transdermal drug delivery systems for the transdermal administration of estrogen, comprising a polymer matrix and estrogen. Methods of making and using such systems also are described.

1. A monolithic transdermal drug delivery system for estradiol, comprising a single polymer matrix layer defining an active surface area and comprising a polymer matrix comprising estradiol as the only drug, wherein the polymer matrix layer has a coat weight selected from the group consisting of 12.5 mg/cm 2  and 15 mg/cm 2 , includes greater than 0.156 mg/cm 2  estradiol, and achieves an estradiol flux that is greater than 0.01 mg/cm 2 /day, based on the active surface area. 
     
     
       2. The transdermal drug delivery system of  claim 1 , wherein the polymer matrix comprises a polymer blend comprising an acrylic adhesive, a silicone adhesive, and soluble polyvinylpyrrolidone (PVP). 
     
     
       3. The transdermal drug delivery system of  claim 1 , wherein the polymer matrix comprises about 2-25% by weight acrylic adhesive, about 45-70% by weight silicone adhesive, about 2-25% by weight soluble PVP, and about 5-15% penetration enhancer, all based on the total dry weight of the polymer matrix. 
     
     
       4. The transdermal drug delivery system of  claim 3 , wherein the penetration enhancer comprises oleyl alcohol. 
     
     
       5. The transdermal drug delivery system of  claim 3 , wherein the penetration enhancer comprises dipropylene glycol. 
     
     
       6. The transdermal drug delivery system of  claim 3 , wherein the penetration enhancer comprises oleyl alcohol and dipropylene glycol. 
     
     
       7. The transdermal drug delivery system of  claim 3 , wherein the acrylic adhesive and silicone adhesive are present in a ratio of from about 1:2 to about 1:6, based on the total weight of the acrylic and silicone adhesives. 
     
     
       8. The transdermal drug delivery system of  claim 1 , wherein the polymer matrix comprises an amount of estradiol effective to deliver a therapeutically effective amount of estradiol over a period of time selected from the group consisting of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days and at least 7 days. 
     
     
       9. The transdermal drug delivery system of  claim 1 , wherein the polymer matrix comprises an amount of estradiol effective to deliver an amount of estradiol selected from the group consisting of about 0.025, 0.0375, 0.05, 0.075 and 0.1 mg/day. 
     
     
       10. A monolithic transdermal drug delivery system for estradiol comprising a single polymer matrix layer comprising estradiol as the only drug, wherein the polymer matrix layer has a coat weight selected from the group consisting of 12.5 mg/cm 2  and 15 mg/cm 2 , and the system has an active surface area that is about 60% of a size selected from the group consisting of 2.5, 3.75, 5.0, 7.5 and 10.0 cm 2  and is effective to deliver an amount of estradiol per day of about 0.025, 0.0375, 0.05, 0.075 and 0.1 mg/day, respectively. 
     
     
       11. A method for administering estradiol, con to the skin or mucosa of a subject in need thereof a monolithic transdermal drug delivery system comprising a single polymer matrix layer defining an active surface area and comprising a polymer matrix comprising estradiol as the only drug, wherein the polymer matrix layer has a coat weight selected from the group consisting of 12.5 mg/cm 2  and 15 mg/cm 2 , includes greater than 0.156 mg/cm 2  estradiol, and achieves an estradiol flux that is greater than 0.01 mg/cm 2 /day, based on the active surface area. 
     
     
       12. The method of  claim 11 , wherein the system has an active surface area that is about 60% of a size selected from the group consisting of 2.5, 3.75, 5.0, 7.5 and 10.0 cm 2  and is effective to deliver an amount of estradiol per day of about 0.025, 0.0375, 0.05, 0.075 and 0.1 mg/day, respectively. 
     
     
       13. A method of making a monolithic transdermal drug delivery system for administering estradiol, comprising forming a polymer matrix comprising estradiol as the only drug and a polymer blend comprising an acrylic adhesive, a silicone adhesive, and soluble PVP, and applying the polymer matrix to a support layer to form a single polymer matrix layer such that the polymer matrix layer has a coat weight selected from the group consisting of 12.5 mg/cm 2  and 15 mg/cm 2  and includes greater than 0.156 mg/cm 2  estradiol. 
     
     
       14. The method of  claim 13 , wherein the system has an active surface area that is about 60% of a size selected from the group consisting of 2.5, 3.75, 5.0, 7.5 and 10.0 cm 2 .